ABSTRACT Thirty-three states and D.C. have enacted medical cannabis laws allowing patients with chronic non-cancer pain to use cannabis, when recommended by a physician, to manage their condition. Policymakers are increasingly considering state medical cannabis laws as a potential solution to the U.S. opioid crisis, with the idea that some patients may substitute cannabis in place of prescription opioids for treatment of chronic non- cancer pain and reduce rates of opioid use disorder and overdose as a result. However, rigorous evidence is lacking: no studies have examined the effects of state medical cannabis laws on opioid-related outcomes among a cohort of patients with chronic non-cancer pain. Further, no existing research has examined how state medical cannabis laws affect chronic non-cancer pain patients? receipt of guideline-concordant non-opioid pain treatments or how such laws affect cannabis use disorder and poisoning among those with chronic non- cancer pain conditions like low back pain or arthritis. Critically, no prior studies have considered how the considerable variation in provisions and implementation across state medical cannabis laws, and within states over time as states amend their laws and change implementation rules, affect outcomes for chronic pain patients. Our study uses a mixed-methods approach incorporating quasi-experimental difference-in-differences analyses; qualitative interviews with state policy and healthcare leaders; and representative surveys of physicians who treat and patients who experience chronic non-cancer pain to fill these research gaps. Using 50-state data sources including Medicare and Optum UnitedHealthcare administrative claims data, we will examine the effects of state medical cannabis laws on receipt of prescription opioid and guideline-concordant non-opioid pharmacologic (e.g., anticonvulsants) and non-pharmacologic (e.g., physical therapy) pain treatments (Aim 1). We will also use these data to examine the effects of state medical cannabis laws on receipt of treatment for opioid use disorder, opioid overdose, cannabis use disorder, and cannabis poisoning among patients with chronic non-cancer pain (Aim 2). We will conduct qualitative interviews with state policy and healthcare system leaders to characterize implementation of state medical cannabis laws for treatment of chronic non-cancer pain (Aim 3). Finally, we will conduct representative surveys with primary care physicians, pain specialists, and patients with chronic non-cancer pain in states with medical cannabis laws. Surveys will capture key attitudes and reported behaviors related to medical cannabis laws, including the degree to which physicians report recommending and patients report using cannabis in place of opioids for treatment of chronic non-cancer pain (Aim 4). In all Aims, we will consider how differences in law provisions and implementation influence chronic pain treatment. Results will yield information needed by state decision-makers considering implementing new medical cannabis laws as well as those considering changes to existing medical cannabis laws? provisions and implementation.